Perihospitalization hemoglobin-epoetin associations in U.S. hemodialysis patients, 1998 to 2003

While hospitalization is common for hemodialysis patients, perihospitalization associations between hemoglobin levels and epoetin doses are not well characterized. U.S. Medicare claims were used to identify 71,360 hemodialysis patients hospitalized from 1998 to 2003. Hemoglobin levels, epoetin doses, and epoetin responsiveness index (ERI) were compared by calendar year. In the prehospitalization month, the mean hemoglobin levels increased from 10.96 g/dL in 1998 to 11.76 in 2003 and the mean epoetin doses from 63,715 to 75,012 U; corresponding values in the hospitalization month were 10.53 and 11.19 g/dL, and 66,623 and 80,569 U. In each year, prehospitalization hemoglobin levels were achieved within 2 months, but ERI declined to prehospitalization levels within 12 months only in 2000. With mixed models, hemoglobin declines in the 3 prehospitalization months grew between 1998 (-0.1362 g/dL/month) and 2003 (-0.2003 g/dL/month). Epoetin responsiveness index slopes were J-shaped, with values of 287.9, 221.1, and 356.5U/month per g/dL in 1998, 2000, and 2003. In the 3 postadmission months, a modest increase in the rapidity of hemoglobin recovery was seen (+0.2538 g/dL/month in 1998, +0.2743 in 2003), with increasing rates of ERI change (+8.7 U/month/g/dL in 1998, +146.8 in 2003). While time to recovery of prehospitalization hemoglobin levels remained constant year to year, epoetin doses and ERI did not, suggesting that optimum perihospitalization anemia management practices have yet to be determined.     

Perihospitalization patterns of hemoglobin levels and erythropoiesis‐stimulating agent doses in US hemodialysis patients, 1998–2009

Anemia management in hemodialysis patients is of primary importance for clinicians and dialysis providers. Through a retrospective claims analysis, we studied prevalent US hemodialysis patients 1998–2009, and examined patterns of hemoglobin levels and erythropoiesis‐stimulating agent (ESA, epoetin [EPO], and darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient claims were used to determine monthly ESA doses and associated hemoglobin levels. ESA dose trajectories were defined with repeated measures models incorporating an autoregressive covariance matrix that compared subsequent measurements with the index month of hospitalization, with variance component covariance matrices chosen for pair‐wise comparisons. Regarding prehospitalization hemoglobin levels, a biphasic pattern occurred in both the EPO (1998–2009, n = 161,242) and DPO (2004–2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter in the EPO population, and fell after 2006 or 2007 in the DPO population. In the EPO population, the proportions of patients with hemoglobin less than 10 g/dL were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of year‐to‐year variability occurred, EPO dose trends were less pronounced, with an apparent peak in 2004 followed by a modest decline; trends were similar for DPO. Trends in EPO dose trajectories did not completely parallel those for hemoglobin level; while EPO doses increased yearly up to 2004, doses stabilized, but did not materially decrease after 2004. No definite annual trends for DPO dose trajectories were apparent.     

Pharmacologic adjuvants to epoetin in the treatment of anemia in patients on hemodialysis

Anemia is a common complication of chronic kidney disease, particularly in patients who are on dialysis. The use of recombinant human erythropoietin has led to the eradication of severe anemia in the dialysis population. Correction of anemia in these patients has been associated with better quality of life and clinical outcomes. Some hemodialysis patients have anemia that either is relatively refractory to epoetin therapy or requires very high doses of epoetin (i.e., hyporesponsiveness), despite having adequate iron stores, and are thus unable to achieve or maintain target hemoglobin levels. Several pharmacologic agents have been studied for effects on improving response to epoetin, either to counter hyporesponsiveness or simply to reduce epoetin use for purely economic reasons. This review examines the available literature regarding the efficacy of these potential pharmacologic adjuvants to epoetin in the treatment of anemia in patients on maintenance hemodialysis, with special emphasis on androgens, vitamin C (ascorbic acid), and L-carnitine. A review of published guidelines and recommendations for use of these agents in hemodialysis patients is provided.     

The effect of a change in epoetin alfa reimbursement policy on anemia outcomes in hemodialysis patients

In 1997, the Health Care Financing Administration Hematocrit Measurement Audit (HMA) program initiated use of a 3-month rolling average hematocrit (Hct) level for reimbursement of epoetin claims in hemodialysis patients, with denial of payment when this value exceeded 36.5%. This study evaluated the impact of the HMA program on anemia-related outcomes in hemodialysis patients. An observational, retrospective study of 987 hemodialysis patients from 11 dialysis centers in the United States was performed, collecting data between October 1996 and December 1997. Centers were selected from a pool of nearly all facilities in the United States, which during May 1997 satisfied one of two criteria: greater than 75% of patients at the facility had mean Hct level of > or =33% (Group A) or fewer than 50% of patients at the facility had mean Hct level of > or =33% (Group B). Each facility maintained its own anemia management practices without specific anemia management interventions as part of this study. Hct level, hemoglobin (Hb) level, and epoetin dose were analyzed to compare the pre-HMA period (October 1996 to May 1997) to the HMA period (June to December 1997) and/or for each of the five quarters of the study period. The primary study endpoint was the percentage of patients with Hct levels of > or =33% during each study quarter. The mean Hct level at baseline was 34% in Group A and 33.4% in Group B (p = 0.01). Hct levels, which were increasing before implementation of the HMA program, decreased during the HMA period (p < 0.001 and p = 0.013 in Groups A and B, respectively). The percentage of patients in Groups A and B with mean quarterly Hct levels of > or =33% decreased during the last quarter of the HMA implementation period compared to the quarter immediately preceding the start of the HMA program (p < 0.001 for both comparisons). Changes in Hb levels were similar to those seen in Hct levels. The mean epoetin dose administered decreased from 13,090 U/week at the start of the study to 11,884 U/week immediately before the HMA program took effect (p < 0.05). The HMA program adversely affected anemia treatment outcomes, regardless of whether dialysis units before HMA implementation had <50% of patients with a Hct level of > or =33% or had >75% of patients with a Hct level of > or =33%. The decline in mean weekly dose of epoetin was likely a result of withholding doses out of concern among providers about risk of reimbursement denial.     

Erythropoietin‐stimulating agents in the management of anemia of end‐stage renal disease patients on regular hemodialysis: A prospective randomized comparative study from Qatar

Despite extensive use, to the best of our knowledge, no trial has simultaneously compared the three currently used erythropoietin‐stimulating agents (ESAs) in a prospective manner in the treatment of anemia of end‐stage renal disease patients. All hemodialysis patients in Qatar who were treated with short‐acting epoetin alfa or beta have been screened. Eligible patients had been prospectively randomized, either to continue on the previous regimen of epoetin or to receive darbepoetin alfa or continuous erythropoietin receptor activator (CERA) for a total period of 40 weeks. All groups were assessed at the end of the study for safety and efficacy parameters. A total of 327 eligible patients were randomized. Mean hemoglobin concentration remained constant within the recommended target range (11–12 g/dL) throughout the study in the three studied groups. The percentage of patients who reached the target range was constantly above 50% in the second half of the study among CERA group patients who also had significantly lower mean number of dose adjustments as compared with the other two groups (P = 0.001). Similarly, the number of discontinuations of ESA among epoetin, darbepoetin, and CERA groups was 17, 19, and 9, respectively (P = 0.042). The frequencies of adverse events were similar in all groups. This study has specifically compared the effect of ESA type on the variability of serum hemoglobin levels in hemodialysis patients. Furthermore, it confirmed the efficacy and safety of once monthly CERA for maintaining tight hemoglobin control within recommended target ranges.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

Determinants of C-reactive protein in chronic hemodialysis patients: relevance of dialysis catheter utilization

Biomarkers of inflammation, especially C-reactive protein (CRP), have been consistently shown to predict poor outcomes in chronic hemodialysis (CHD) patients. However, the determinants of CRP and the value of its monitoring in CHD patients have not been well defined. We conducted a retrospective cohort study to evaluate possible determinants of the inflammatory response in CHD patients with a focus on dialysis catheter utilization. Monthly CRP were measured in 128 prevalent CHD patients (mean age 56.6 years [range 19-90], 68% African Americans, 39% diabetics [DM]) over a mean follow-up of 12 months (range 2-26 months). There were a total of 2405 CRP measurements (median 5.7 mg/L; interquartile range [IQR] 2.4-16.6 mg/L). The presence of a dialysis catheter (p<0.002), cardiovascular disease (p=0.01), male gender (p=0.005), higher white blood cell count (p<0.0001), elevated phosphorus (p=0.03), and lower cholesterol (p=0.02) and albumin (p<0.0001) concentrations were independent predictors of elevated CRP in the multivariate analysis. Additionally, CRP levels were significantly associated with the presence of a catheter, when comparing the levels before and after catheter insertion (p=0.002) as well as before and after catheter removal (p=0.009). Our results indicate that the presence of a hemodialysis catheter is an independent determinant of an exaggerated inflammatory response in CHD patients representing a potentially modifiable risk factor.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Correlates affecting survival in chronic hemodialysis patients: The combined impact of albumin and high hemoglobin levels on improving outcomes,local and national results

While national mortality rates for end‐stage renal disease (ESRD) patients remain high, for the past 4 years, lower than expected local mortality rates have been consistently seen in our facilities. Because of these progressive improvements in mortality rates, a study of 687 hemodialysis patients over a 4‐year period, 2003 through 2006, was undertaken to analyze which factors may be contributing to the enhanced survival rates. We also examined the partially overlapping United States Renal Data System clinical performance measures national data sets of hemodialysis patients for 2001 to 2004. Proportional hazards and logistic regression models were used to determine significant predictors of short‐term survival. Variables tested included hemoglobin (Hb), albumin, calcium, phosphorus, infections, hospitalizations, URR, Kt/V, erythropoietic stimulating agents (epoetin‐α) use, and comorbid conditions. The local and national models identified albumin, Hgb, and hospitalization as statistically significant predictors of survival. Local models also found years of dialysis as a significant predictor. Locally, there was a 69‐fold increase from 16.1 deaths/1000 patient years for albumin ≥4.0 with Hgb≥14.0 to 1115.9 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. The increase nationally is a 4‐fold increase from 96 deaths/1000 patient‐years for albumin ≥4.0 with Hgb≥14.0 to 406 deaths/1000 patient‐years for albumin <3.5 with Hgb<11.0. There was no evidence that higher erythropoietic stimulating agents dose levels were associated with higher mortality rates, independent of the other significant factors. In conclusion, the findings indicate that individually higher Hgb and albumin levels are associated with increased survival, and when higher Hgb levels are in association with high albumin levels, the survival rates and hospitalizations are synergistically improved.     

Challenges and limitations of maintenance hemodialysis in urban South India

Maintenance hemodialysis is a treatment modality available to few patients reaching end-stage renal disease in India. However, the morbidity and outcome of such treatment remains largely unknown. A retrospective cohort of patients commencing hemodialysis in a secondary care institution in India between January 1, 2002 and December 31, 2004 was studied. Patient demographics, cardiac status, access, hospitalizations, and emergency room visits were assessed and outcomes determined. During the study period, 95 patients (66 males, 29 females) commenced maintenance hemodialysis. The underlying cause of chronic kidney disease was diabetic nephropathy in 66.3% of patients. Cumulative follow-up was 676+9.1 patient months. The mean serum creatinine (+SD) at initiation of dialysis was 8.39+3.28 mg%. Thirty-six percent of patients had a functioning arteriovenous fistula at commencement of dialysis, while the remaining 64% of patients required temporary access. The mean number of comorbidities was 1.9+1.0/patient; diastolic dysfunction was deemed to be present in 20.4% of the patients. The hospitalization rate was 3.9/patient year; the number of visits to the emergency room was 4.9/patient year. Cardiac pathology was the most common cause leading to hospitalization and emergency room visits. Diabetic patients were older and had higher cardiac morbidity (p<0.01). The outcome was as follows: 39% transferred to other units; 27% died; 9% switched to CAPD; 8% lost to follow-up; 1% transplantation: Kaplan-Meier survival analysis showed a median survival of 410 days. Patients commencing hemodialysis in an urban dialysis center in South India are predominantly male and have significant comorbidity including diabetes and cardiac disease. Outcome is generally poor. Hence, a huge opportunity for improvement exists.     

D‐dimer levels in maintenance hemodialysis patients: High prevalence of positive values also in the group without predisposing diseases

We aimed to estimate the prevalence of elevated D‐dimer levels in all chronic hemodialysis patients and those without additional disease, and to identify factors associated with increased D‐dimer. In 167 chronic hemodialysis patients from our center, D‐dimer was measured before dialysis. The effects of age, C‐reactive protein (CRP), recent acute illness, vascular access, anticoagulation type, dialysis vintage, and chronic diseases, considered to predispose for increased D‐dimer levels, were analyzed. The median D‐dimer in the whole group was 966 (inter‐quartile range [IQR] 524–1947) μg/L and was positive (>500 μg/L) in 75% of cases. D‐dimer was positive in 91% of patients with acute illness, 76% of those with predisposing chronic diseases, but was still positive in 52% of patients without additional disease (i.e., acute illness or predisposing chronic diseases) – median D‐dimer was 538.5 (IQR 359–966) μg/L. D‐dimer was correlated to patients' age, but not dialysis vintage. In univariate analysis, the D‐dimer levels were significantly higher in patients with atrial fibrillation, ischemic heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and on citrate anticoagulation. Multivariate logistic regression showed that only age >65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07) were independently associated with positive D‐dimer at 500 μg/L cut‐off, while the significance of age disappeared at 2000 μg/L cut‐off. To conclude, the high prevalence of positive D‐dimer values even in hemodialysis patients without additional disease limits the use of D‐dimer for exclusion of thromboembolic diseases in hemodialysis patients.     

Hyperprolactinemia in end‐stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. Methods: The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in‐center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health‐related quality of life, self‐reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12‐month follow‐up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. Findings: Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th–75th percentile 48–195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. Discussion: Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one‐year period.     

Intensive In-Center Hemodialysis for Children: A Case for Longer Dialysis Duration

Background:  Children with renal failure need their dialysis time optimized. Although traditional surrogate markers of outcome in pediatric patients have been growth and development, increasing attention is being focused on cardiovascular risk factors, such as hypertension, volume overload, malnutrition, and elevated calcium (Ca) and phosphorus (P) levels. We have previously shown catch-up growth without growth hormone, in children undergoing long intermittent hemodialysis. Recently we analyzed retrospectively cardiovascular risk factors in patients treated with this regimen.
Methods:  Patients starting dialysis between 1997 and 2001 and on dialysis at least 6 months were evaluated. Charts were reviewed for Ca, P, parathyroid hormone (PTH), albumin, hemoglobin and blood pressure levels, Ca intake, blood pressure medications, dialysis time, and clearance and ultrafiltration rates. Means were calculated for 6- month intervals, up to 36 months.
Results:  Mean equilibrated dialyzer Kt/V _urea ranged from 1.9 to 2.1, and mean weekly dialysis time for oliguric patients varied from 14.8 to 16.3 hr, with average hourly ultrafiltration rates from 0.3 to 0.4 L. Mean values for P and Ca × P were below 1.8 mM and 4.4 mmol   ² /L ² , respectively. Mean hemoglobin levels were 115 to 126 g/L, albumin 39 to 41 g/L, and PTH 156 to 231 pg/mL. Most patients had normal predialysis blood pressures.
Conclusions:  In this pediatric cohort, intensive center hemodialysis was associated with excellent growth, nutrition, Ca, P, and anemia control and reasonable blood pressure values. Large multicenter studies are needed to better determine optimal dialysis therapy for children.     

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross‐sectional, 1‐year,retrospective cohort study

Introduction This study aimed to evaluate the association between proton pump inhibitor (PPI) use and serum magnesium levels, and the role of hypomagnesemia and PPI use as a risk factor for mortality in hemodialysis patients. Methods An observational study, including a cross‐sectional and 1‐year retrospective cohort study. The study comprised 399 hemodialysis patients at a single center, and was conducted from January to September 2014. Multiple linear regression analysis was used to investigate the independent relationship between serum magnesium levels and baseline demographic and clinical variables, including PPI and histamine‐2 receptor antagonist use. Cox regression model was used to identify lower serum magnesium level and PPI as a predictor of 1‐year mortality. Findings Serum magnesium levels were lower with PPI use than non‐PPI use (2.39 ± 0.36 vs. 2.56 ± 0.39 mg/dL, P < 0.001). Multiple linear regression analysis showed that PPI use, low serum albumin levels, and low serum potassium and high‐sensitivity C‐reactive protein (hs‐CRP) levels were significantly associated with low serum magnesium levels. A total of 29 deaths occurred during the follow‐up period. According to Cox regression analysis stratified by hs‐CRP, only high serum hs‐CRP levels (>4.04 mg/L) in association with low serum magnesium levels was an independent risk factor for 1‐year mortality (hazard ratio: 2.92; 95% CI: 1.53–6.40, P < 0.001). Discussion Serum magnesium levels are lower in PPI use. In the inflammatory state, a low serum magnesium level is a significant predictor of mortality in hemodialysis patients.     

Erythropoietic agents, iron and hemoglobin—What happens beyond the trial setting: Observational data from the ANZDATA Registry

Background: The issues surrounding anemia management in patients receiving dialysis therapy are complex and widely debated. Although numerous trials have been published, clinical practice patterns may differ, particularly in the presence of uncertainty about the optimal management of anemia in this setting. Methods: We examined data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) regarding use of erythropoietic agents (EA), hemoglobin, and ferritin concentrations and transferrin saturation in 8476 prevalent dialysis patients in Australia and New Zealand during the 6 months preceding March 31, 2001. From this cross‐sectional survey, we examined the distribution of reported hemoglobin concentration, transferrin saturation, and ferritin concentration. Among hemodialysis patients, other predictors of hemoglobin examined included urea reduction ratio (URR), age, sex, and the presence of comorbidities. Results: In Australia, 87% of dialysis patients received an EA; in contrast, only 42% of New Zealand patients received an EA. Hemoglobin concentrations were significantly higher in Australia, where 16% of reported values were <100 g/L, compared to New Zealand where 37% reported values were <100 g/L. Transferrin saturation and serum ferritin concentrations were significantly correlated, but less strongly among those receiving EA than those not receiving these agents. Both transferrin saturation and serum ferritin were significantly and independently associated with hemoglobin concentration, as were age and sex. The association with ferritin was inverse: higher serum ferritin concentrations were associated with lower hemoglobin concentrations. There was poor agreement (κ = 0.15) between categories of low transferrin saturation (<20%) and low ferritin concentrations (<200 ng/mL). Among the Australian hemodialysis patients, there was no significant variation in Hb between categories where reported URR was ≥65%, whereas the group with a reported URR <65% had a significantly lower hemoglobin concentration. Conclusions: There was a wide variation in reported hemoglobin concentrations in this population. Potential contributing factors include variable patient responsiveness to EA and iron, differing regulations in Australia and New Zealand regarding government subsidy of EA, and the lack of consensus among physicians regarding hemoglobin target values. Although a cross‐sectional study cannot directly address the predictive value of iron indices for iron deficiency, it appears likely that transferrin and ferritin have different relationships with hemoglobin, and measurement of both may have greater clinical utility than either parameter alone.     

The impact of education and cooking methods on serum phosphate levels in patients on hemodialysis: 1‐year study

Introduction: Control of serum phosphate is important for patients on hemodialysis. The aim of the study was to determine if education based on phosphorus‐reducing techniques in food preparation and thermal processing, and accordingly prepared and applied diets, will lead to better outcomes than a standard education program to improve phosphate control in patients on hemodialysis. Methods: Forty‐seven patients on hemodialysis were divided between an intervention and a control group. All subjects received training about nutrition for hemodialysis patients by trained dietitian. In addition, subjects in the intervention group received additional training in phosphorus‐reducing techniques in food preparation and received two hospital meals prepared using suggested cooking methods to reduce the phosphate content of food during dialysis treatment. Serum phosphate, serum albumin, and anthropometric parameters were measured, while nPCR was calculated, at the baseline and during the 1‐year study. Findings: No differences in serum phosphate levels were observed between intervention (1.68 mmol/L [1.48–2.03]) and control group (1.88 mmol/L [1.57–2.2]) at baseline (P = 0.130). Although not statistically significant between groups the mean reduction was more apparent in the intervention group (?0.3 mmol/L (?0.4 to 0.1) vs. ?0.2 (?0.5 to 0.1)), and lead to significantly reduction of phosphate binder therapy. During the study, the nPCR and anthropometric status of the patients did not change significantly. Discussion: Providing additional education to hemodialysis patients on the specific cooking methods and accordingly prepared meals may decrease serum phosphate levels without significantly affecting nutritional status which may be useful in helping to prevent and treat hyperphosphatemia.     

Dialysis patients treated with Epoetin α show improved exercise tolerance and physical function: A new analysis of the Canadian Erythropoietin Study Group trial

The risks/benefits of anemia treatment in dialysis patients have been redefined in the US Epoetin α label. This analysis was carried out to determine if increasing hemoglobin (Hb) levels improve exercise tolerance and physical function in anemic dialysis patients. This is a new analysis of the Canadian Erythropoietin Study Group trial, a double‐blind, randomized, placebo‐controlled trial in dialysis patients. Subjects were 18 to 75 years old, on hemodialysis for >3 months, and had a baseline Hb <9.0 g/dL. Patients with a history of diabetes mellitus, ischemic heart disease, or severe/uncontrolled hypertension were excluded. Patients were randomized to receive Epoetin α to a target Hb of 9.5 to 11.0 g/dL (n=40) or a target of 11.5 to 13.0 g/dL (n=38), or receive placebo (n=40). Results from patients in the Epoetin‐α–treated arms were combined for this analysis. Hb level, exercise tolerance (Treadmill Stress Test and 6‐Minute Walk Test) and patient‐reported physical function measures (Physical Summary domain from the Kidney Disease Questionnaire, and 4 domains from the Sickness Impact Profile) were reported at baseline and months 2, 4, and 6. Differences in measures were statistically significant for exercise tolerance (Treadmill Stress, P=0.0001) and patient‐reported physical function (Kidney Disease Questionnaire Physical, P=0.0001; Sickness Impact Profile Physical, P=0.0015) across all time points for Epoetin‐α–treated patients compared with placebo. Improvements were seen at 2 months and were maintained through months 4 and 6. Dialysis patients receiving Epoetin α showed improved exercise tolerance and physical function. These findings should be considered as physicians weigh the risks and benefits of treatment.     

Does online hemodiafiltration lead to reduction in trace elements and vitamins?

Hemodiafiltration (HDF) has been reported to improve nutritional intake, but as it increases convective losses, it could also increase micronutrient loss. We prospectively audited the effect of HDF on vitamin B12, zinc and selenium. Thirty‐four patients dialyzing (T/Th/Sa) switched to HDF, and 44 dialyzing (M/W/F) remained on high‐flux hemodialysis (HD) and were followed for 12 months. Dialysis adequacy, weight, hemoglobin, and serum albumin did not differ between the groups and did not change over 12 months’ follow up. Similarly, vitamin B12 did not differ: HDF, 443 (325–682) ng/mL HD vs. 478 (327–690) ng/mL HDF; 6 months, 513 (351–664) ng/mL vs. 460 (379–647) ng/mL; or 12 months, 444 (317–617) ng/mL vs. 492 (323–644) ng/mL. And no patient had subnormal values. Folate levels, in those not taking supplements, were also stable (start, 6.2 ± 0.7 μg/L HD vs. 7.2 ± 1.0 μg/L HDF; 12 months, 6.5 ± 0.9 μg/L vs. 10.9 ± 2.4 μg/L). Serum zinc was subnormal in 50% prior to switching to HDF, 10.4 ± 0.4 μmol/L, but did not fall with HDF 10.2 ± 0.3 μmol/L; similarly, selenium was low in 49% prior to switching to HDF, 0.77 ± 0.06 μmol/L, but remained stable on HDF, 0.82 ± 0.06 μmol/L. Although HDF adds convective clearance to standard hemodialysis, it does not lead to a reduction in vitamin B12, folate, zinc, or selenium. However, half of this dialysis cohort had low levels of both zinc and selenium.     

Determinants of metabolic acidosis among hemodialysis patients

Metabolic acidosis is frequently present, poorly controlled, and associated with adverse effects among hemodialysis patients. Potential determinants of metabolic acidosis include endogenous acid production, administration of alkali, neutralization of acid by buffers, dilution of serum bicarbonate by interdialytic fluid gain, and loss of bicarbonate in stool. Understanding the relative importance of these determinants may help guide efforts to manage metabolic acidosis. We used chart abstraction, patient interviews, and laboratory testing to assess variables related to acid production (protein breakdown), alkali administration (dialysis dose, missed treatments, dialysate bicarbonate concentration, oral bicarbonate supplements), acid buffering (phosphorus binders), dilution of bicarbonate (interdialytic weight gain), and loss of bicarbonate in stool (diarrhea) for 190 randomly selected patients from 44 hemodialysis facilities. We used multivariate analyses to determine which potential determinants were independently associated with predialysis serum bicarbonate levels. Of all patients, 30% had metabolic acidosis (serum bicarbonate level <22 mEq/L). On multivariate analysis, metabolic acidosis was more likely with increased protein nitrogen appearance (odds ratio [OR] 1.60 per 0.2 g/kg/day, p=0.001) and less likely with increased Kt/V (OR 0.61 per 0.20 increase in Kt/V, p<0.001) and with increased calcium carbonate use (OR 0.38 per 2 g/day, p=0.003). Key determinants of metabolic acidosis among hemodialysis patients are protein breakdown, dialysis dose, and specific phosphorus binders. Further work is needed to develop interventions to address these determinants.     

A Comparative Study of C‐Reactive Protein Plasma Levels in Patients on Hemodialysis and Peritoneal Dialysis

In dialysis patients, C‐reactive protein (CRP), a well‐recognized marker of inflammation, predicts mortality. Higher levels have been described in hemodialysis (HD) patients as compared with peritoneal dialysis (PD) patients. Our aim was to determine, based on CRP plasma levels, the degree of inflammation in HD patients using low‐permeability polysulfone membranes and relatively pure dialysate, and that in PD patients. A secondary objective was to study factors associated with hypoalbuminemia and inflammation in both populations. We studied 69 stable patients on dialysis (32 on HD and 37 on PD). The mean age was 69.9 ± 8.2 years, and the mean time on dialysis was 27 months. The two populations were comparable for overall and cardiovascular comorbidities. Nephelometry was used to measure CRP plasma levels (normal levels < 0.6 mg/dL). The Kt/V_urea, corrected for residual renal clearance, and the equivalent of protein nitrogen appearance (PNA) were also calculated. Of the patients studied, 53% showed CRP plasma levels higher than 0.6 mg/dL; in 36%, the levels were higher than 1 mg/dL. No significant differences in these percentages were noted between the two dialysis groups. Patients with CRP levels higher than 1 mg/dL showed lower serum albumin, iron, hemoglobin, and transferrin levels, and higher ferritin values and leukocyte counts. Under logistic regression analysis, CRP levels higher and lower than 1 mg/dL were significantly associated with serum albumin [p = 0.01; odds ratio (OR): 0.15], iron (p = 0.006; OR: 0.96), transferrin (p = 0.004; OR: 0.97), and hemoglobin (p = 0.02; OR: 0.67). Serum albumin levels were significantly lower in PD patients. Under regression analysis, serum albumin levels correlated with cholesterol (r: 0.25; p = 0.04), serum iron (r: 0.5; p = 0.0001), transferrin (r: 0.3; p = 0.015), ultrafiltration capacity (r: 0.42; p = 0.008), and CRP values above 0.6 mg/dL (r: –0.65; p = 0.001). In conclusion, the frequent elevation of CRP plasma levels observed in both HD and PD patients suggests the presence of a silent inflammatory state. Hemodialysis performed with biocompatible, low‐permeability membranes is not associated with higher CRP plasma levels than those seen in PD. In both groups, hypoalbuminemia is related to CRP level. Levels of serum albumin, slightly lower in PD patients, are also related to peritoneal ultrafiltration capacity.